GLP-1R agonists are novel new drugs for patients with type 2 diabetes mellitus (T2DM). An intriguing connection between these agents such as liraglutide and native GLP-1 from the gut and the release of the blood pressure lowering cardiac hormone atrial natriuretic peptide (ANP) establishes a new gut – heart connection not only for glycemic control in diabetes, but in overall cardiovascular homeostasis.